The severity of the acute ischemic stroke (AIS) related disability is highly variable, and thought to depend on age, infarct size/location, and history of cardiovascular disease (CVD, coronary artery disease, hypertension etc). There is a critical need to improve upon existing approaches used in the evaluation and therapeutic management of AIS to lower AIS related disability. The cardiovascular (CV) system plays a critical role in the severity of post stroke outcome, as increased aortic stiffness (AS) and sympathetic activity are predictors of stroke outcome. Further, an understanding of the integrated CV response, i.e., the ability of the autonomic nervous system to adjust arterial and cardiac function, to maintain adequate cerebral perfusion to the infarct area, may enhance our ability to predict poor AIS outcomes. However, the utility of assessing the acute changes in AS, cardiac function, and autonomic control during an AIS event as a predictor of stroke outcome or recommended immediate treatment has not been examined. Our immediate goal is to examine the physiological changes that occur during AIS as potential life-saving predictors of stroke outcome and potential targets for acute therapy with AIS. Specifically, we will measure autonomic and CV changes in patients shortly after onset of AIS followed by 30-day post-AIS evaluation of functional outcome (modified Rankin). In parallel we will measure comparable physiological changes with surgically-induced AIS in a rodent model of CVD, the obese Zucker rat (OZR). The OZR is an excellent translational model of CVD stemming from its hyperphagic development of obesity, insulin resistance, dyslipidemia and moderate hypertension. Many of these CVD risk factors are evident in stroke patients. We will incorporate in-vivo and ex-vivo assessments of CV structure/function before, and post AIS. Our analogous studies in humans and rodents provide an optimal opportunity to dissect pathophysiological mechanisms that contribute to stroke outcome in patients. These data will advance our understanding of the CV responses to stroke and provide the basis for improved clinical management of stroke. This approach may help alleviate the rising healthcare costs of cerebral vascular disease, projected to be $818 billion by 2030.